この博士論文は内容の要約のみの公開（または一部非公開）になっています筑波大学 (University of Tsukuba)201

SY  LUAN CAO

Tsukuba Repository

Prominence of nestin-expressing Schwann-like
cells in the bone marrow of myelodysplastic
syndromes with severe fibrosis
著者（英） SY  LUAN CAO
内容記述 この博士論文は内容の要約のみの公開（または一部
非公開）になっています
year 2019
その他のタイトル 線維化を伴う骨髄異形成症候群患者の骨髄ではネス
チン陽性シュワン細胞様構造が異常増殖している
学位授与大学 筑波大学 (University of Tsukuba)
学位授与年度 2018
報告番号 12102甲第9202号
URL http://hdl.handle.net/2241/00156489
論  文  概  要 
○ 論 文 題 目
Prominence of nestin-expressing Schwann-like cells in the bone
marrow of myelodysplastic syndromes with severe fibrosis
(線維化を伴う骨髄異形成症候群患者の骨髄ではネスチン陽性シュ
ワン細胞様構造が異常増殖している)
○ 指 導 教 員
人間総合科学研究科 Clinical Sciences 専攻   千葉 滋 教授
         （所  属）  筑波大学大学院人間総合科学研究科 Clinical Sciences  専攻 
    （氏  名）   CAO SY LUAN 
目    的： 
Nestin-expressing stromal cells (NESCs) and Schwann cells in the bone marrow (BM) play 
crucial roles as a niche for normal hematopoietic stem cells in mice. Both of these types of 
cells were reportedly decreased in myeloproliferative neoplasms (MPN) patients and also in 
a mouse model. Conversely, an increase in NESCs was reported in acute myeloid leukemia. 
Accordingly, it is of interest whether and how these BM stromal cells are structured in 
myelodysplastic syndromes (MDS). In this study, we focused on NESCs and glial fibrillary 
acidic protein (GFAP)-expressing stromal cells in the BM of MDS patients. 
対象と方法： 
Forty-five patients with MDS, and 16 patients with MPN divided into two groups as MPN-
associated MF (12 cases) and chronic myelogenous leukemia (CML) (4 cases) were 
enrolled in the study. Samples from 17 patients with non-Hodgkin lymphoma (NHL) 
without BM involvement were analyzed as the control. We used archived formalin-fixed 
paraffin-embedded (FFPE) BM biopsy samples from these patients for silver staining and 
immunostaining, and mononuclear frozen cells BM aspirate samples for genetic analysis. 
Immunostaining were performed with antibodies against nestin, CD34, α-smooth muscle 
actin (α-SMA), GFAP, neurofilament heavy chain (NFH), and others. 
結    果： 
We identified 19 (42.2%) MDS with fibrosis (MDS-F) cases, 7 (15.5%) had fibrosis grade 
3 (MF3) and 12 (26.7%) had MF2, and 26 (57.8%) remaining patients identified as MDS 
without fibrosis (MDS w/o F), 11 (24.5%) were MF1, and 15 (33.3%), as MF0. The 12 
MPN-associated MF cases were evaluated as MF2 or MF3. We found a marked increase of 
NESCs in MDS-F patients at a high frequency (9/19; 47.4%), but not in MDS w/o F (0/26; 
0%) and MPN (0/12; 0%) patients, including both MPN-associated MF and CML. In 8 of 
the 9 MDS-F cases (88.9%) with the NESC increase, a majority of NESCs also expressed 
GFAP, with an additional increase in GFAP single-positive cells. Furthermore, in 7 of 
them, we found a prominent structure characterized by NFH staining surrounded by NESCs 
with GFAP expression or GFAP single-positive cells. 
考    察： 
Our findings suggest that increase of NESCs in BM of MDS-F patients may have an 
important role in promotion of BM myelofibrosis. According to immunostaining results, 
NESCs expressing the GFAP may represent the rejuvenated Schwann cells that start to 
proliferate with some stimulation in MDS-F, but not in MPN-associated MF. Therefore, 
nestin may have a potential marker to distinguish MDS-F and MPN-associated MF. In 
addition, it is reasonable to hypothesize that the abnormally enhanced Schwann cell 
proliferation induces axonal extension. Consequently, the increase in nestin-expressing 
Schwann-like cells in the BM is likely to have a significance in the pathophysiology of 
myelofibrosis in patients with MDS. 
結    論： 
We have identified a unique subgroup of MDS-F characterized by the abnormal 
proliferation of a structure comprising terminal nerve axons and the surrounding Schwann-
like cells, typically accompanying severe fibrosis and hypercellular BM. This structure 
could have a relevance to the pathophysiology of MDS-F. 
  


線維化を伴う骨髄異形成症候群患者の骨髄ではネスチン陽性シュワン細胞様構造が異常増殖している

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線維化を伴う骨髄異形成症候群患者の骨髄ではネスチン陽性シュワン細胞様構造が異常増殖している

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